Lenticular glutathione synthesis: rate-limiting factors in its regulation and decline.

Six factors were analyzed which may be involved in the decline of glutathione synthesis in the aging lens and cataract, with special emphasis placed upon the human lens. The factors included: 1) lability of gamma-glutamylcysteine synthetase, 2) paucity of gamma-glutamylcysteine synthetase in primate lenses as compared to other mammalian lenses, 3) enzyme activity reduction with age in the human lens, 4) rate control by reactant scarcity, especially of cysteine and magnesium ion, 5) rate control by inhibition using 5'-AMP, 5'-ADP and glutathione, and 6) possible dissociation of the multi-enzyme complex. It was concluded that decline of the glutathione synthetic capacity in vivo would be most likely caused by reduction of gamma-glutamylcysteine synthetase activity rather than of glutathione synthetase activity.